The Genetics of Nicotine Addiction

Researchers at the University of Iowa have identified
certain genetic profiles that may be linked to a person’s risk for developing
nicotine addiction and other psychological behaviors. Using a genome-wide scan,
scientists analyzed blood samples from smokers versus nonsmokers and found
similar genetic patterns among smokers that may one day be used as a genetic
test to determine who may be more vulnerable to nicotine addiction.

Smoking signs: Scientists at the University of Iowa have discovered a genetic profile in smokers that may determine a person’s risk of developing nicotine addiction.

“When you look at substance-abuse
disorders and antisocial behavior, these are the last vestiges of the belief
that mental impairments are related to moral will,” says Tracy Gunter, director
of forensic psychiatry at the University
of Iowa and a coauthor of
the study. “And one of the exciting things in this work is [that] it’s
beginning to form ideas that folks with these disorders are biologically
different.”

In the past few
years, researchers around the world have zeroed in on various genetic regions
believed to be involved in one’s vulnerability to addiction. Some have studied
genes that control certain neurotransmitters in the brain, while others have
looked at genes related to addictive traits like risk taking and impulsivity.
Gunter and her colleagues chose to look at the genome as a whole and observe
which genes are turned on and which turned off in people with a long history of
smoking.

“One gene itself
doesn’t tell you whether you have a disorder,” says Robert Philibert, a
University of Iowa professor of psychiatry and the study’s lead author. “But if
you measure 30 or 40, you come up with a good risk. So what we do is spot the
biology.”

In this latest study, published in the American Journal of Medical Genetics, Philibert and his colleagues analyzed the
DNA samples of 94 people, some smokers and some nonsmokers. Using a technique
called transcriptional profiling, they looked at all 30,000 genes of the human
genome, fluorescently labeling those that were turned on versus those that were
turned off in both groups. What they found was both promising and daunting: 579
genes were more activated and 584 other genes were less activated in smokers
versus nonsmokers.

“This is sort of
like shining a light in a tomb,” says Philibert. “It says there’s a lot here,
but it doesn’t tell you anything about it. In order to really explore the
biology, people will have to replicate this.”

Gunter adds that few psychological behaviors exist alone.
For example, people who smoke may also have panic disorders or depression, each
of which may involve a number of different genes. “How do you sort that out?” Gunter asks. “Is a genetic test disorder- specific, or specific to a cluster of
disorders? There may be some sites that contribute more to prediction of a
disorder than other sites. In the years to come, could we prune that down?
Maybe.”

There’s also a question of whether, once a person starts
smoking, increased nicotine consumption causes certain genes to turn on or off.
To that end, Philibert plans to run similar genome-wide analyses on younger
people who have not yet started smoking but may have a family history of
nicotine dependence. He will also analyze DNA samples from patients with single
psychological diagnoses to obtain what he calls a “cleaner phenotype.”

Anthony Hinrichs, assistant professor of psychiatry at
Washington University, in St. Louis, studies genes that code for certain
nicotine receptors in the brain. He sees this latest approach as casting a wide
net for other potentially related genes.

“Transcriptional
profiling in general, and this study in particular, are very promising ways of
nominating candidate genes,” says Hinrichs. “I’m sure that these genes will now
be on the map for other investigators.”

However, Hinrichs believes it will be a while before
scientists can design accurate genetic tests for such disorders. “So far, researchers have identified a number
of genetic markers which may increase susceptibility to drug addiction,” says
Hinrichs. “Any of these would only increase the risk of addiction by a small
percentage. We certainly have a long way to go before we can routinely use
genetic tests.”

Meanwhile, Gunter and Philibert recognize that this kind of genetic
testing comes with a host of ethical questions.

“There are some
people [to whom] you may be able to say on a genetic basis, ‘You should never
take the first drink,’” says Gunter. “And some will listen, and some may not.
But it may have more impact on somebody if you are able to say, ‘This is why
you, as an individual, don’t need to take the first drink: because you are at a
particular risk for this to become a dependency, and this is how we know.’ That’s
different from taking a profile and saying, ‘This is another alcoholic; I’m not
going to insure them.’ Our part in this is to inform them of the level of their
risk so it’s truly an informed choice.”